Congenital plasminogen deficiency is caused by mutations in PLG, the gene coding for production of the zymogen plasminogen, and is an ultrarare disorder associated with abnormal accumulation or growth of fibrin-rich pseudomembranous lesions on mucous membranes. Left untreated, these lesions may impair organ function and impact quality of life. Plasminogen replacement therapy should provide an effective treatment of the manifestations of congenital plasminogen deficiency. An open-label phase 2/3 study of human Glu-plasminogen administered IV at 6.6 mg/kg every 2 to 4 days in 15 patients with congenital plasminogen deficiency is ongoing. Reported here are data on 14 patients who completed at least 12 weeks of treatment. The primary end point was an increase in trough plasminogen activity levels by at least an absolute 10% above baseline. The secondary end point was clinical success, defined as ≥50% improvement in lesion number/size or functionality impact from baseline. All patients achieved at least an absolute 10% increase in trough plasminogen activity above baseline. Clinical success was observed in all patients with clinically visible (conjunctiva and gingiva), nonvisible (nasopharynx, bronchus, colon, kidney, cervix, and vagina), and wound-healing manifestations of the disease. Therapeutic effects were rapid, as all but 2 lesions resolved or improved after 4 weeks of treatment. Human Glu-plasminogen was well tolerated in both children and adults. This study provides critical first evidence of the clinical utility of ongoing replacement therapy with human Glu-plasminogen for the treatment of children and adults with congenital plasminogen deficiency. This trial was registered at www.clinicaltrials.gov as #NCT02690714.

中文翻译：

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纤溶酶原替代疗法用于治疗先天性纤溶酶原缺乏症的儿童和成人

先天性纤溶酶原缺乏症是由 PLG（编码酶原纤溶酶原产生的基因）突变引起的，是一种极罕见的疾病，与粘膜上富含纤维蛋白的假膜病变的异常积累或生长有关。如果不治疗，这些病变可能会损害器官功能并影响生活质量。纤溶酶原替代疗法应能有效治疗先天性纤溶酶原缺乏症的表现。在 15 名先天性纤溶酶原缺乏症患者中，每 2 至 4 天静脉注射 6.6 毫克/千克人 Glu 纤溶酶原的开放标签 2/3 期研究正在进行中。这里报告的是 14 名完成至少 12 周治疗的患者的数据。主要终点是谷型纤溶酶原活性水平比基线增加至少绝对 10%。次要终点是临床成功，定义为病变数量/大小或功能影响比基线改善≥50%。所有患者的谷型纤溶酶原活性均达到基线以上至少 10% 的绝对增加。在所有具有临床可见（结膜和牙龈）、不可见（鼻咽、支气管、结肠、肾、宫颈和阴道）和伤口愈合表现的患者中均观察到临床成功。治疗效果很快，因为在治疗 4 周后，除 2 个病灶外，所有病灶都消退或改善。儿童和成人对人 Glu-纤溶酶原的耐受性良好。该研究提供了持续的人类 Glu-纤溶酶原替代疗法用于治疗先天性纤溶酶原缺乏症的儿童和成人的临床效用的重要第一证据。